uLorazepam sold under thebrand name Ativan amongothers is abenzodiazepine medication is used to treat anxiety disorders, trouble sleeping,active seizures including status epilepticus.uIts also used for surgery tointerfere with memory formation and to sedate those who are being mechanically ventilated.uBenzodiazepines are a class of psychoactive drugswhose core chemical structure is the combination of a benzene ring and a diazepine ring. Benzodiazepines enhance the effect of theneurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor,resulting in sedative, hypnotic, anti-anxiety, anticonvulsant, and musclerelaxant propertiesuLorazepam was initially patented in 1963, Ativan oraltablets, made by Valeant Pharmaceuticals, were approved by the Food and DrugAdministration (FDA) 30th of September1977 and went on sale in theUnited States thesame year.uIt is on theWorld Health Organization’s List of Essential Medicines asone of the most effectiveand safe medicines needed in a health system.uWholesale cost in thedeveloping world of a typical dose by mouth is between US$0.02 and US$0.
16 asof 2014. In the United States as of 2015 a typical month supply isless than US$25. uIn the UnitedStates by 2011 28 million prescriptions for lorazepam were filled makingit the second most prescribed benzodiazepine after alprazolamuLorazepam was initially patented in 1963, Ativan oraltablets, made by Valeant Pharmaceuticals, were approved by the Food and DrugAdministration (FDA) 30th of September1977 and went on sale in theUnited States thesame year.
uIt is on theWorld Health Organization’s List of Essential Medicines asone of the most effectiveand safe medicines needed in a health system.uWholesale cost in thedeveloping world of a typical dose by mouth is between US$0.02 and US$0.16 asof 2014. In the United States as of 2015 a typical month supply isless than US$25.
uIn the UnitedStates by 2011 28 million prescriptions for lorazepam were filled makingit the second most prescribed benzodiazepine after alprazolamuLorazepam is accessible in the form of tablets and are available instrengths of 0.5 mg, 1 mg, and 2 mg.uAtivan can also be injected intravenously or intramuscularlythough, theintravenous route is preferred. Care should be taken to avoid injection into smallveins and intra-arterial injection.uAbsorption from theinjection site is considerably slower if the intramuscular route is used and asrapid an effect may be obtained by oral administration of lorazepam.u A 1:1 dilution of Ativan Injection with normal saline orSterile Water for Injection BP is recommended in order to facilitateintramuscular administrationfor intravenousadministration, Ativan Injection should always be diluted with saline orSterile Water for Injection BP as a 1:1 dilution.uLorazepam could also be administered sublingually andtrans dermallyuLorazepam is highlyprotein bound and is extensively metabolized into pharmacologically inactive metabolites due to its poorlipid solubility itsabsorbed relativelyslowly by mouth and is unsuitable for rectal administration.
uHowever, its poorlipid solubility and high degree of protein binding (85-90%) mean itsvolume of distribution is mainly the vascular compartment, causing relativelyprolonged peak effects. This contrasts with the highly lipid-soluble diazepam,which, although rapidly absorbed orally or rectally, soon redistributes fromthe serum to other parts of the body, in particular, body fat. uThis explains whyone lorazepam dose, despite its shorter serum half-life, has more prolongedpeak effects than an equivalent diazepam dose.Lorazepam is rapidlyconjugated at its 3-hydroxy group into lorazepam glucuronide which is thenexcreted in the urine.
uLorazepam glucuronidehas no demonstrable CNS activity in animals. The plasma levels of lorazepam areproportional to the dose given. There is no evidence of accumulation oflorazepam on administration up to six months.
On regular administration,diazepam will accumulate, since it has a longer half-life and activemetabolites, these metabolites also have long half-livesuRelative to other benzodiazepines, lorazepam isthought to have high affinity for GABA receptors,which may alsoexplain its marked amnesic effects.u Its mainpharmacological effects are the enhancement of the effects of theneurotransmitter GABA at the GABAA receptor. Benzodiazepines,such as lorazepam, enhance the effects of GABA at the GABAA receptor viaincreasing the frequency of opening of the chloride ion channel on the GABAA receptors; which resultsin the therapeutic actions of benzodiazepines.u They, however,do not on their own enhance the GABAA receptors, butrequire the neurotransmitter GABA to be present. Thus, the effect of The magnitudeand duration of lorazepam effects are dose-related, meaning larger doses havestronger and longer-lasting effects, because the brain has spare benzodiazepinedrug receptor capacity, with single, clinical doses leading only to anoccupancy of some 3% of the available receptors.uTheanticonvulsant properties of lorazepam and other benzodiazepines may be, inpart or entirely, due to binding to voltage-dependent sodium channels ratherthan benzodiazepine receptors.
uUsual adult dose for anxiety: Tablets:Initial dose is normally 2 to 3 mg orallyper day administered 2 to 3 times per day and1 to 2 mg orally 2 to 3 times a day for maintenance. If taken intravenously then 2 mg total, or 0.044 mg/kg, whichever is smaller.
uUsual adult dose for insomnia: 2-4 mg orallyadministered at bedtime and the dosage shouldbe increased gradually when needed to help avoid adverse effects.uUsual pediatric dose for anxiety: similar to adult doseuUsual pediatric dose for insomnia: similar to adult dose. For elderly ordebilitated patients, an initial dosage of 1 to 2 mg/day in divided dosesis recommended.The dose of injection should be reduced by 50% when Co-administered withprobenecid or valproate.
it may be necessary to increase the dose in femalepatients who are taking oral contraceptivesalonguLorazepam metabolises differently compared to otherbenzodiazepines as its metabolised in the liver through the process of glucuronidation.uBenzodiazepines that metabolise through glucuronidation- no activemetabolites and they are rarely susceptible to drug-drug interactions unlikeother benzos such as diazepam which are metabolised through the cytochrome p450u Blood concentrations of unconjugated lorazepam peakat 1-4 h, significant concentrations persisting for 24 h and decreasing slowlyover the next 24 h. u About 95% of a dose of lorazepam was accounted for in urineand faeces over a period of 5 days, 74.5% was excreted in the urine as lorazepamglucuronide and 13.
5% as minor metabolites. The excretory half-life was 12 h.uThe biological half-life of lorazepam is 10–20 hours.
uLorazepam are commonlyprescribed for a wide range of conditions, including use as sleep aides, musclerelaxants, and anxiolytics. However, dose-related side effects can be seen,including amnesia and central respiratory depression. Other drugs including opioids,alcohol, and over-the-counter sleep aids can have additive or synergistic effects on the centralnervous system and respiratory function. Certain subpopulationsof patients can have significant and severe benzo-mediatedeffects. The prudent clinician should weigh the risksand benefits of these agents before prescribing